Cabozantinib-s-malate or Sunitinib Malate in Treating Patients With Previously Untreated Locally Advanced or Metastatic Kidney Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01835158
• Collaborator: (none)
• Enrollment: 157
• Locations: 488
• Arms: 2
• Patients Per Site: 0.3

Study Details

Study Description

Brief Summary

This randomized phase II trial studies how well cabozantinib-s-malate works compared to sunitinib malate in treating patients with previously untreated kidney cancer that has spread from where it started to nearby tissue or lymph nodes or to other places in the body. Cabozantinib-s-malate and sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether cabozantinib-s-malate is more effective than sunitinib malate in treating patients with kidney cancer.

Condition or Disease	Intervention/Treatment	Phase
Clear Cell Renal Cell Carcinoma; Metastatic Kidney Carcinoma; Stage III Renal Cell Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7	Drug: Cabozantinib S-malate; Other: Laboratory Biomarker Analysis; Drug: Sunitinib Malate	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine if patients with renal cancer treated with cabozantinib (cabozantinib-s-malate) will have improved progression-free survival compared to patients treated with sunitinib (sunitinib malate).

SECONDARY OBJECTIVES:

1. To determine whether the response rate of patients with renal cancer treated with cabozantinib will be higher when compared with patients treated with sunitinib.

2. To determine whether patients with renal cancer treated with cabozantinib will have an improved overall survival when compared with patients treated with sunitinib.

TERTIARY OBJECTIVES:

1. To determine whether renal cancer patients with high MET expression by immunohistochemistry (IHC) have improvement in progression-free survival compared to patients with low MET expression on both arms of this study.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive cabozantinib-s-malate orally (PO) once daily (QD) for 6 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive sunitinib malate PO QD for 4 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 157 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase II Study Comparing Cabozantinib (NSC #761968) With Commercially Supplied Sunitinib in Patients With Previously Untreated Locally Advanced or Metastatic Renal Cell Carcinoma
• Actual Study Start Date: Jul 8, 2013
• Actual Primary Completion Date: Apr 18, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I (cabozantinib-s-malate) Patients receive cabozantinib-s-malate PO QD for 6 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.	Drug: Cabozantinib S-malate; Given PO; Other Names: BMS-907351 Cabometyx Cometriq XL-184 XL184 ; Other: Laboratory Biomarker Analysis; Correlative studies
Active Comparator: Arm II (sunitinib malate) Patients receive sunitinib malate PO QD for 4 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Sunitinib Malate; Given PO; Other Names: SU011248 SU11248 sunitinib Sutent

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) [Up to 5 years]

   Progression free survival (PFS) was investigator assessed and is measured from the beginning of treatment until patient progression or death. Progression was determined using RECIST 1.1 criteria, progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).The primary analysis will be based on the stratified log-rank statistic to compare the two treatment arms on PFS. The Kaplan-Meier product-limit estimator will be used to estimate PFS distributions.Progression Free Survival was assessed per investigator, as this was the protocol-specified endpoint, and both investigator and independent review analyses of the PFS endpoint have been published

2. Overall Survival (OS) [Up to 5 years]

   The primary analysis will be based on the stratified log-rank statistic to compare the two treatment arms on OS. The Kaplan-Meier product-limit estimator will be used to estimate OS distributions.

Secondary Outcome Measures

1. Objective Response Rates [Up to 5 years]

   Objective response rates (ORR) was investigator assessed. ORR is the rate of complete or partial responses, based on RECIST 1.1 criteria. A response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. The Fisher exact test will be used to compare the two treatment arms.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Renal cell carcinoma with some component of clear cell histology; histologic documentation of metastatic disease is not required

• Locally advanced (defined as disease not amenable to curative surgery or radiation therapy) or metastatic renal cell carcinoma (RCC) (equivalent to stage IV RCC, according to American Joint Committee on Cancer [AJCC] staging)

• Eligible patients must be intermediate/poor risk, per the International Metastatic Renal Cell Carcinoma (mRCC) Database Consortium (Heng) criteria; patients must therefore have as one or more of the following six factors:

• Time from diagnosis of RCC to systemic treatment < 1 year

• Note: systemic treatment refers to the initiation of A031203 protocol treatment

• Hemoglobin < the lower limit of normal (LLN)

• Corrected calcium > the upper limit of normal (ULN)

• Karnofsky performance status < 80%

• Neutrophil count > ULN

• Platelet count > ULN

• No radiographic evidence of cavitating pulmonary lesion(s)

• No tumor invading the inferior vena cava (IVC) or superior vena cava (SVC) blood vessels

• No evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days prior to registration

• No prior systemic treatment for RCC; supportive therapies such as bisphosphonates (zoledronic acid) or denosumab are permitted

• Patients must not have had a major surgical procedure or significant traumatic injury within 6 weeks prior to study registration, and must have fully recovered from any such procedure; however, patients who have had a nephrectomy may be enrolled 4 weeks after surgery, providing there are no wound-healing complications; the following are not considered to be major procedures: thoracentesis, paracentesis, port placement, laparoscopy, thoracoscopy, bronchoscopy, endoscopic ultrasonographic procedures, mediastinoscopy, skin biopsies, incisional biopsies, imaging-guided biopsy for diagnostic purposes, and routine dental procedures

• Radiation:

• To the brain, thoracic cavity, abdomen, or pelvis must be completed at least 90 days before registration;

• To bone must be completed at least 14 days before registration; and

• To any other sites must be completed at least 28 days before registration In all cases, there must be complete recovery and no ongoing complications from prior radiation therapy

• No chronic concomitant treatment of strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers or inhibitors; patients may not have received a strong CYP3A4 inducer within 12 days prior to registration nor a strong CYP3A4 inhibitor within 7 days prior to registration

• Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria; lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 2 cm with conventional techniques or as >= 1 cm with spiral computed tomography (CT) scan

• No active brain metastases; patients with treated, stable brain metastases for at least three months are eligible as long as they meet the following criteria:

• Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 3 months, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or CT); (stable dose of anticonvulsants are allowed); treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, linear accelerator [LINAC], or equivalent) or a combination as deemed appropriate by the treating physician; patients with central nervous system (CNS) metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to registration are not eligible

• Baseline brain imaging (MRI/CT) is required

• No serious non-healing wound, ulcer, or bone fracture requiring intervention within 28 days prior to registration

• No arterial thrombotic events within 6 months prior to registration, including transient ischemic attack (TIA), cerebrovascular accident (CVA), peripheral arterial thrombus, unstable angina or angina requiring surgical or medical intervention in the 6 months prior to registration, or myocardial infarction (MI); patients with clinically significant peripheral artery disease (i.e., claudication on less than one block), significant vascular disease (i.e., aortic aneurysm, history of aortic dissection), or any other arterial thrombotic event are ineligible

• No history of pulmonary embolism or untreated deep venous thrombosis (DVT) within 6 months prior to registration; note: patients with recent DVT who have been treated with therapeutic anticoagulation with low molecular weight heparin for at least 6 weeks are eligible; patients receiving therapeutic warfarin (> 2 mg/day) are not eligible; patients on warfarin may be switched to low molecular weight heparin at the discretion of the treating physician

• No inadequately controlled hypertension (defined as a blood pressure of >= 150 mmHg systolic and/or >= 90 mmHg diastolic), or any prior history of hypertensive crisis or hypertensive encephalopathy

• No New York Heart Association (NYHA) class >= 2 congestive heart failure

• Ejection fraction on echocardiogram (Echo) or multi gated acquisition scan (MUGA) > 50%

• No corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before randomization; note: if initial QTcF is found to be > 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed; if the average of these three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regard

• No history of congenital QT syndrome

• No unstable cardiac arrhythmia within 6 months prior to registration

• No evidence of any of the following:

• Clinically-significant gastrointestinal bleeding within 6 months before registration; or

• Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 3 months before registration; or

• Any other signs indicative of pulmonary hemorrhage within 3 months before registration

• No history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within 6 months prior to registration and complete healing/resolution prior to registration; no percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months prior to registration

• No active peptic ulcer disease, within 28 days before registration

• No inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis within 28 days before registration

• No malabsorption syndrome within 28 days before registration

• No uncompensated hypothyroidism; patients with hypothyroidism on therapy are required to have thyroid stimulating hormone (TSH) within normal limits

• No radiologic or clinical evidence of pancreatitis

• No history of organ transplant

• Patients with active infection requiring systemic treatment within 28 days prior to registration are not eligible

• Patients who are pregnant or nursing are not eligible; women of child bearing potential must have a negative serum or urine pregnancy test within 16 days prior to registration; women of child-bearing potential include:

• Any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea >= 12 consecutive months)

• Women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level > 35m IU/mL

• Women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy)

• Performance status: Eastern Cooperative Oncology Group (ECOG) 0-2

• Archival tissue must be available for submission, though it is optional for patients to choose to participate in the correlative sub studies

• Absolute neutrophil count (ANC) >= 1,500/uL

• Platelet count >= 100,000/uL

• Hemoglobin >= 9 g/dL; patients may not have had a transfusion within 7 days prior to screening assessment

• Total bilirubin =< 1.5 x upper limits of normal

• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN

• Albumin >= 2.8 g/dL

• Serum creatinine =< 1.5 x ULN, OR calculated creatinine clearance >= 30 mL/minute (modified Cockcroft and Gault formula)

• Urine protein to creatinine (UPC) ratio < 1.0; if UPC >= 1, then a 24-hour urine protein must be assessed; eligible patients must have a 24-hour urine protein value < 1 g

• Total serum calcium < 12 mg/dL

• International normalized ratio (INR) =< 1.2 x ULN; subjects receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation

• TSH within normal limits (WNL); TSH only required for patients on thyroid supplementation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Southern Cancer Center PC-Providence	Mobile	Alabama	United States	36608
2	Alaska Breast Care and Surgery LLC	Anchorage	Alaska	United States	99508
3	Alaska Women's Cancer Care	Anchorage	Alaska	United States	99508
4	Anchorage Oncology Centre	Anchorage	Alaska	United States	99508
5	Katmai Oncology Group	Anchorage	Alaska	United States	99508
6	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
7	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
8	Community Cancer Institute	Clovis	California	United States	93611
9	University Oncology Associates	Clovis	California	United States	93611
10	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
11	San Diego VA Medical Center	San Diego	California	United States	92161
12	UCSF Medical Center-Mount Zion	San Francisco	California	United States	94115
13	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado	United States	80012
14	The Medical Center of Aurora	Aurora	Colorado	United States	80012
15	Boulder Community Hospital	Boulder	Colorado	United States	80301
16	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado	United States	80304
17	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
18	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado	United States	80907
19	Porter Adventist Hospital	Denver	Colorado	United States	80210
20	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
21	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado	United States	80218
22	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado	United States	80218
23	SCL Health Saint Joseph Hospital	Denver	Colorado	United States	80218
24	Rocky Mountain Cancer Centers-Rose	Denver	Colorado	United States	80220
25	Rose Medical Center	Denver	Colorado	United States	80220
26	Western States Cancer Research NCORP	Denver	Colorado	United States	80222
27	Mercy Medical Center	Durango	Colorado	United States	81301
28	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado	United States	80113
29	Swedish Medical Center	Englewood	Colorado	United States	80113
30	Mountain Blue Cancer Care Center	Golden	Colorado	United States	80401
31	North Colorado Medical Center	Greeley	Colorado	United States	80631
32	Rocky Mountain Cancer Centers-Greenwood Village	Greenwood Village	Colorado	United States	80111
33	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado	United States	80228
34	Saint Anthony Hospital	Lakewood	Colorado	United States	80228
35	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado	United States	80120
36	Littleton Adventist Hospital	Littleton	Colorado	United States	80122
37	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado	United States	80124
38	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
39	Longmont United Hospital	Longmont	Colorado	United States	80501
40	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado	United States	80501
41	McKee Medical Center	Loveland	Colorado	United States	80539
42	Parker Adventist Hospital	Parker	Colorado	United States	80138
43	Rocky Mountain Cancer Centers-Parker	Parker	Colorado	United States	80138
44	Saint Mary Corwin Medical Center	Pueblo	Colorado	United States	81004
45	Rocky Mountain Cancer Centers - Pueblo	Pueblo	Colorado	United States	81008
46	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado	United States	80260
47	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
48	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut	United States	06105
49	Middlesex Hospital	Middletown	Connecticut	United States	06457
50	Beebe Medical Center	Lewes	Delaware	United States	19958
51	Christiana Gynecologic Oncology LLC	Newark	Delaware	United States	19713
52	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware	United States	19713
53	Helen F Graham Cancer Center	Newark	Delaware	United States	19713
54	Medical Oncology Hematology Consultants PA	Newark	Delaware	United States	19713
55	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
56	Beebe Health Campus	Rehoboth Beach	Delaware	United States	19971
57	TidalHealth Nanticoke / Allen Cancer Center	Seaford	Delaware	United States	19973
58	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware	United States	19801
59	MedStar Georgetown University Hospital	Washington	District of Columbia	United States	20007
60	MedStar Washington Hospital Center	Washington	District of Columbia	United States	20010
61	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224-9980
62	Memorial Health University Medical Center	Savannah	Georgia	United States	31404
63	Pali Momi Medical Center	'Aiea	Hawaii	United States	96701
64	Queen's Cancer Center - Pearlridge	'Aiea	Hawaii	United States	96701
65	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii	United States	96813
66	Queen's Medical Center	Honolulu	Hawaii	United States	96813
67	Straub Clinic and Hospital	Honolulu	Hawaii	United States	96813
68	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
69	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii	United States	96817
70	Queen's Cancer Center - Kuakini	Honolulu	Hawaii	United States	96817
71	Castle Medical Center	Kailua	Hawaii	United States	96734
72	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii	United States	96766
73	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	United States	83706
74	Kootenai Medical Center	Coeur d'Alene	Idaho	United States	83814
75	Kootenai Cancer Center	Post Falls	Idaho	United States	83854
76	Kootenai Cancer Clinic	Sandpoint	Idaho	United States	83864
77	Rush - Copley Medical Center	Aurora	Illinois	United States	60504
78	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
79	Illinois CancerCare-Bloomington	Bloomington	Illinois	United States	61704
80	Illinois CancerCare-Canton	Canton	Illinois	United States	61520
81	Memorial Hospital of Carbondale	Carbondale	Illinois	United States	62902
82	Illinois CancerCare-Carthage	Carthage	Illinois	United States	62321
83	Centralia Oncology Clinic	Centralia	Illinois	United States	62801
84	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
85	Weiss Memorial Hospital	Chicago	Illinois	United States	60640
86	Carle on Vermilion	Danville	Illinois	United States	61832
87	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois	United States	62526
88	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
89	Heartland Cancer Research NCORP	Decatur	Illinois	United States	62526
90	Carle Physician Group-Effingham	Effingham	Illinois	United States	62401
91	Crossroads Cancer Center	Effingham	Illinois	United States	62401
92	Illinois CancerCare-Eureka	Eureka	Illinois	United States	61530
93	Illinois CancerCare-Galesburg	Galesburg	Illinois	United States	61401
94	Western Illinois Cancer Treatment Center	Galesburg	Illinois	United States	61401
95	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois	United States	61443
96	Illinois CancerCare-Macomb	Macomb	Illinois	United States	61455
97	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois	United States	61938
98	Garneau, Stewart C MD (UIA Investigator)	Moline	Illinois	United States	61265
99	Porubcin, Michael MD (UIA Investigator)	Moline	Illinois	United States	61265
100	Spector, David MD (UIA Investigator)	Moline	Illinois	United States	61265
101	Trinity Medical Center	Moline	Illinois	United States	61265
102	Holy Family Medical Center	Monmouth	Illinois	United States	61462
103	Illinois CancerCare-Monmouth	Monmouth	Illinois	United States	61462
104	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
105	Community Cancer Center Foundation	Normal	Illinois	United States	61761
106	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
107	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois	United States	61350
108	Radiation Oncology of Northern Illinois	Ottawa	Illinois	United States	61350
109	Illinois CancerCare-Pekin	Pekin	Illinois	United States	61554
110	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
111	Proctor Hospital	Peoria	Illinois	United States	61614
112	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
113	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois	United States	61615
114	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
115	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
116	Illinois CancerCare-Peru	Peru	Illinois	United States	61354
117	Valley Radiation Oncology	Peru	Illinois	United States	61354
118	Illinois CancerCare-Princeton	Princeton	Illinois	United States	61356
119	Memorial Medical Center	Springfield	Illinois	United States	62781
120	Carle Cancer Center	Urbana	Illinois	United States	61801
121	The Carle Foundation Hospital	Urbana	Illinois	United States	61801
122	Rush-Copley Healthcare Center	Yorkville	Illinois	United States	60560
123	Elkhart Clinic	Elkhart	Indiana	United States	46514-2098
124	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana	United States	46514
125	Elkhart General Hospital	Elkhart	Indiana	United States	46515
126	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana	United States	46845
127	Community Howard Regional Health	Kokomo	Indiana	United States	46904
128	IU Health La Porte Hospital	La Porte	Indiana	United States	46350
129	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana	United States	46360
130	Woodland Cancer Care Center	Michigan City	Indiana	United States	46360
131	Memorial Regional Cancer Center Day Road	Mishawaka	Indiana	United States	46545
132	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana	United States	46545
133	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana	United States	46545
134	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana	United States	46563
135	Reid Health	Richmond	Indiana	United States	47374
136	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
137	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana	United States	46601
138	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States	46628
139	Michiana Hematology Oncology PC-Westville	Westville	Indiana	United States	46391
140	McFarland Clinic PC - Ames	Ames	Iowa	United States	50010
141	Constantinou, Costas L MD (UIA Investigator)	Bettendorf	Iowa	United States	52722
142	University of Iowa Healthcare Cancer Services Quad Cities	Bettendorf	Iowa	United States	52722
143	Mercy Hospital	Cedar Rapids	Iowa	United States	52403
144	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
145	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa	United States	50325
146	Mercy Cancer Center-West Lakes	Clive	Iowa	United States	50325
147	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
148	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa	United States	50309
149	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
150	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa	United States	50314
151	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
152	Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
153	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
154	Iowa City VA Healthcare System	Iowa City	Iowa	United States	52246
155	Siouxland Regional Cancer Center	Sioux City	Iowa	United States	51101
156	Mercy Medical Center-Sioux City	Sioux City	Iowa	United States	51102
157	Saint Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
158	Methodist West Hospital	West Des Moines	Iowa	United States	50266-7700
159	Mercy Medical Center-West Lakes	West Des Moines	Iowa	United States	50266
160	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
161	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
162	Cancer Center of Kansas - El Dorado	El Dorado	Kansas	United States	67042
163	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
164	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
165	Cancer Center of Kansas-Kingman	Kingman	Kansas	United States	67068
166	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
167	Cancer Center of Kansas-Liberal	Liberal	Kansas	United States	67905
168	Cancer Center of Kansas-Manhattan	Manhattan	Kansas	United States	66502
169	Cancer Center of Kansas - McPherson	McPherson	Kansas	United States	67460
170	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
171	Cancer Center of Kansas - Parsons	Parsons	Kansas	United States	67357
172	Cancer Center of Kansas - Pratt	Pratt	Kansas	United States	67124
173	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
174	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
175	Associates In Womens Health	Wichita	Kansas	United States	67208
176	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
177	Ascension Via Christi Hospitals Wichita	Wichita	Kansas	United States	67214
178	Cancer Center of Kansas - Wichita	Wichita	Kansas	United States	67214
179	Wichita NCI Community Oncology Research Program	Wichita	Kansas	United States	67214
180	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
181	Oncology Hematology Care Inc-Crestview	Crestview Hills	Kentucky	United States	41017
182	University of Kentucky/Markey Cancer Center	Lexington	Kentucky	United States	40536
183	Ochsner Medical Center Jefferson	New Orleans	Louisiana	United States	70121
184	Harold Alfond Center for Cancer Care	Augusta	Maine	United States	04330
185	Eastern Maine Medical Center	Bangor	Maine	United States	04401
186	Penobscot Bay Medical Center	Rockport	Maine	United States	04856
187	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland	United States	21237
188	MedStar Montgomery Medical Center	Olney	Maryland	United States	20832
189	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
190	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
191	Boston Medical Center	Boston	Massachusetts	United States	02118
192	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
193	Bixby Medical Center	Adrian	Michigan	United States	49221
194	Hickman Cancer Center	Adrian	Michigan	United States	49221
195	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan	United States	48106
196	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
197	Beaumont Hospital - Dearborn	Dearborn	Michigan	United States	48124
198	Henry Ford Hospital	Detroit	Michigan	United States	48202
199	Ascension Saint John Hospital	Detroit	Michigan	United States	48236
200	Green Bay Oncology - Escanaba	Escanaba	Michigan	United States	49829
201	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
202	Hurley Medical Center	Flint	Michigan	United States	48503
203	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan	United States	49801
204	Allegiance Health	Jackson	Michigan	United States	49201
205	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
206	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
207	Borgess Medical Center	Kalamazoo	Michigan	United States	49048
208	Sparrow Hospital	Lansing	Michigan	United States	48912
209	Saint Mary Mercy Hospital	Livonia	Michigan	United States	48154
210	Mercy Memorial Hospital	Monroe	Michigan	United States	48162
211	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan	United States	48162
212	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
213	Lake Huron Medical Center	Port Huron	Michigan	United States	48060
214	Ascension Saint Mary's Hospital	Saginaw	Michigan	United States	48601
215	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
216	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota	United States	56601
217	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
218	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
219	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
220	Unity Hospital	Fridley	Minnesota	United States	55432
221	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
222	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
223	Saint John's Hospital - Healtheast	Maplewood	Minnesota	United States	55109
224	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
225	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
226	Minneapolis VA Medical Center	Minneapolis	Minnesota	United States	55417
227	Health Partners Inc	Minneapolis	Minnesota	United States	55454
228	New Ulm Medical Center	New Ulm	Minnesota	United States	56073
229	North Memorial Medical Health Center	Robbinsdale	Minnesota	United States	55422
230	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905
231	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota	United States	56303
232	Saint Cloud Hospital	Saint Cloud	Minnesota	United States	56303
233	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota	United States	55416
234	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
235	Regions Hospital	Saint Paul	Minnesota	United States	55101
236	United Hospital	Saint Paul	Minnesota	United States	55102
237	Saint Francis Regional Medical Center	Shakopee	Minnesota	United States	55379
238	Lakeview Hospital	Stillwater	Minnesota	United States	55082
239	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
240	Rice Memorial Hospital	Willmar	Minnesota	United States	56201
241	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota	United States	55125
242	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri	United States	63628
243	Cox Cancer Center Branson	Branson	Missouri	United States	65616
244	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
245	Southeast Cancer Center	Cape Girardeau	Missouri	United States	63703
246	Veterans Administration	Columbia	Missouri	United States	65201
247	Capital Region Southwest Campus	Jefferson City	Missouri	United States	65109
248	Freeman Health System	Joplin	Missouri	United States	64804
249	Mercy Hospital Joplin	Joplin	Missouri	United States	64804
250	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri	United States	65401
251	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri	United States	65401
252	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
253	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
254	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
255	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
256	Cancer Research for the Ozarks NCORP	Springfield	Missouri	United States	65804
257	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
258	CoxHealth South Hospital	Springfield	Missouri	United States	65807
259	Missouri Baptist Sullivan Hospital	Sullivan	Missouri	United States	63080
260	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri	United States	63127
261	Billings Clinic Cancer Center	Billings	Montana	United States	59101
262	Saint Vincent Healthcare	Billings	Montana	United States	59101
263	Montana Cancer Consortium NCORP	Billings	Montana	United States	59102
264	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
265	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
266	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
267	Saint Peter's Community Hospital	Helena	Montana	United States	59601
268	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
269	Montana Cancer Specialists	Missoula	Montana	United States	59802
270	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
271	Community Medical Hospital	Missoula	Montana	United States	59804
272	Nebraska Hematology and Oncology	Lincoln	Nebraska	United States	68506
273	Nebraska Cancer Research Center	Lincoln	Nebraska	United States	68510
274	Faith Regional Health Services Carson Cancer Center	Norfolk	Nebraska	United States	68701
275	Great Plains Health Callahan Cancer Center	North Platte	Nebraska	United States	69101
276	Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
277	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
278	Alegent Health Immanuel Medical Center	Omaha	Nebraska	United States	68122
279	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
280	Nebraska Cancer Specialists - Omaha	Omaha	Nebraska	United States	68124
281	Alegent Health Lakeside Hospital	Omaha	Nebraska	United States	68130
282	Oncology Hematology West PC	Omaha	Nebraska	United States	68130
283	Creighton University Medical Center	Omaha	Nebraska	United States	68131
284	Regional West Medical Center Cancer Center	Scottsbluff	Nebraska	United States	69361
285	Cancer and Blood Specialists-Henderson	Henderson	Nevada	United States	89052
286	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada	United States	89052
287	Las Vegas Cancer Center-Henderson	Henderson	Nevada	United States	89052
288	21st Century Oncology-Henderson	Henderson	Nevada	United States	89074
289	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada	United States	89074
290	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
291	Cancer and Blood Specialists-Shadow	Las Vegas	Nevada	United States	89106
292	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada	United States	89106
293	21st Century Oncology	Las Vegas	Nevada	United States	89109
294	HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway	Las Vegas	Nevada	United States	89109
295	HealthCare Partners Medical Group Oncology/Hematology-San Martin	Las Vegas	Nevada	United States	89113
296	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada	United States	89119
297	Cancer Therapy and Integrative Medicine	Las Vegas	Nevada	United States	89121
298	21st Century Oncology-Vegas Tenaya	Las Vegas	Nevada	United States	89128
299	Cancer and Blood Specialists-Tenaya	Las Vegas	Nevada	United States	89128
300	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada	United States	89128
301	HealthCare Partners Medical Group Oncology/Hematology-Tenaya	Las Vegas	Nevada	United States	89128
302	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada	United States	89144
303	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada	United States	89148-2405
304	21st Century Oncology-Fort Apache	Las Vegas	Nevada	United States	89148
305	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89148
306	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada	United States	89148
307	HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills	Las Vegas	Nevada	United States	89149
308	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada	United States	89169
309	Nevada Cancer Research Foundation NCORP	Las Vegas	Nevada	United States	89169
310	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire	United States	03301
311	LRGHealthcare-Lakes Region General Hospital	Laconia	New Hampshire	United States	03246
312	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
313	Solinsky Center for Cancer Care	Manchester	New Hampshire	United States	03103
314	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey	United States	07920
315	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
316	Englewood Hospital and Medical Center	Englewood	New Jersey	United States	07631
317	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
318	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
319	Hematology Oncology Associates of Central New York-Auburn	Auburn	New York	United States	13021
320	Montefiore Medical Center-Einstein Campus	Bronx	New York	United States	10461
321	Montefiore Medical Center-Weiler Hospital	Bronx	New York	United States	10461
322	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467
323	Maimonides Medical Center	Brooklyn	New York	United States	11219
324	Veterans Affairs Western New York Health Care System-Buffalo	Buffalo	New York	United States	14215
325	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
326	Memorial Sloan Kettering Commack	Commack	New York	United States	11725
327	Hematology Oncology Associates of Central New York-East Syracuse	East Syracuse	New York	United States	13057
328	Glens Falls Hospital	Glens Falls	New York	United States	12801
329	Northwell Health/Center for Advanced Medicine	Lake Success	New York	United States	11042
330	Hematology Oncology Associates of Central New York-Liverpool	Liverpool	New York	United States	13088
331	North Shore University Hospital	Manhasset	New York	United States	11030
332	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11040
333	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
334	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
335	NYP/Weill Cornell Medical Center	New York	New York	United States	10065
336	Hematology Oncology Associates of Central New York-Rome	Rome	New York	United States	13440
337	Memorial Sloan Kettering Sleepy Hollow	Sleepy Hollow	New York	United States	10591
338	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
339	Hematology Oncology Associates of Central New York-Onondaga Hill	Syracuse	New York	United States	13215
340	Memorial Sloan Kettering Nassau	Uniondale	New York	United States	11553
341	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
342	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina	United States	28328
343	Duke University Medical Center	Durham	North Carolina	United States	27710
344	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina	United States	27534
345	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
346	Hendersonville Hematology and Oncology at Pardee	Hendersonville	North Carolina	United States	28791
347	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina	United States	28791
348	AdventHealth Hendersonville	Hendersonville	North Carolina	United States	28792
349	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina	United States	28546
350	Vidant Oncology-Kinston	Kinston	North Carolina	United States	28501
351	FirstHealth of the Carolinas-Moore Regional Hospital	Pinehurst	North Carolina	United States	28374
352	Iredell Memorial Hospital	Statesville	North Carolina	United States	28677
353	Southeast Clinical Oncology Research Consortium NCORP	Winston-Salem	North Carolina	United States	27104
354	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
355	Sanford Bismarck Medical Center	Bismarck	North Dakota	United States	58501
356	Sanford Broadway Medical Center	Fargo	North Dakota	United States	58122
357	Sanford Clinic North-Fargo	Fargo	North Dakota	United States	58122
358	Sanford Roger Maris Cancer Center	Fargo	North Dakota	United States	58122
359	Altru Cancer Center	Grand Forks	North Dakota	United States	58201
360	Strecker Cancer Center-Belpre	Belpre	Ohio	United States	45714
361	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio	United States	43402
362	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
363	Oncology Hematology Care Inc-Eden Park	Cincinnati	Ohio	United States	45202
364	Oncology Hematology Care Inc-Mercy West	Cincinnati	Ohio	United States	45211
365	Oncology Hematology Care Inc-Anderson	Cincinnati	Ohio	United States	45230
366	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio	United States	45236
367	Oncology Hematology Care Inc-Blue Ash	Cincinnati	Ohio	United States	45242
368	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
369	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio	United States	43214
370	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
371	Columbus NCI Community Oncology Research Program	Columbus	Ohio	United States	43215
372	Grant Medical Center	Columbus	Ohio	United States	43215
373	The Mark H Zangmeister Center	Columbus	Ohio	United States	43219
374	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
375	Doctors Hospital	Columbus	Ohio	United States	43228
376	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
377	Miami Valley Hospital	Dayton	Ohio	United States	45409
378	Miami Valley Hospital North	Dayton	Ohio	United States	45415
379	Dayton NCI Community Oncology Research Program	Dayton	Ohio	United States	45459
380	Delaware Health Center-Grady Cancer Center	Delaware	Ohio	United States	43015
381	Delaware Radiation Oncology	Delaware	Ohio	United States	43015
382	Grady Memorial Hospital	Delaware	Ohio	United States	43015
383	Oncology Hematology Care Inc-Healthplex	Fairfield	Ohio	United States	45014
384	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
385	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
386	Wayne Hospital	Greenville	Ohio	United States	45331
387	Kettering Medical Center	Kettering	Ohio	United States	45429
388	Fairfield Medical Center	Lancaster	Ohio	United States	43130
389	Lancaster Radiation Oncology	Lancaster	Ohio	United States	43130
390	Lima Memorial Hospital	Lima	Ohio	United States	45804
391	Marietta Memorial Hospital	Marietta	Ohio	United States	45750
392	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio	United States	43537
393	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio	United States	43537
394	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
395	Licking Memorial Hospital	Newark	Ohio	United States	43055
396	Newark Radiation Oncology	Newark	Ohio	United States	43055
397	Saint Charles Hospital	Oregon	Ohio	United States	43616
398	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio	United States	43616
399	Southern Ohio Medical Center	Portsmouth	Ohio	United States	45662
400	Springfield Regional Medical Center	Springfield	Ohio	United States	45505
401	ProMedica Flower Hospital	Sylvania	Ohio	United States	43560
402	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
403	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio	United States	43606
404	Saint Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
405	University of Toledo	Toledo	Ohio	United States	43614
406	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio	United States	43617
407	Mercy Health - Saint Anne Hospital	Toledo	Ohio	United States	43623
408	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio	United States	43623
409	Upper Valley Medical Center	Troy	Ohio	United States	45373
410	Fulton County Health Center	Wauseon	Ohio	United States	43567
411	Saint Ann's Hospital	Westerville	Ohio	United States	43081
412	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio	United States	43701
413	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma	United States	73505
414	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
415	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma	United States	73120
416	Natalie Warren Bryant Cancer Center at Saint Francis	Tulsa	Oklahoma	United States	74136
417	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma	United States	74146
418	Warren Clinic Oncology-Tulsa	Tulsa	Oklahoma	United States	74146
419	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
420	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
421	Providence Newberg Medical Center	Newberg	Oregon	United States	97132
422	Providence Willamette Falls Medical Center	Oregon City	Oregon	United States	97045
423	Providence Portland Medical Center	Portland	Oregon	United States	97213
424	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
425	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
426	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania	United States	18201
427	Geisinger Cancer Services-Pottsville	Pottsville	Pennsylvania	United States	17901
428	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania	United States	18840
429	Geisinger Medical Group	State College	Pennsylvania	United States	16801
430	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania	United States	18711
431	AnMed Health Cancer Center	Anderson	South Carolina	United States	29621
432	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina	United States	29316
433	Medical University of South Carolina	Charleston	South Carolina	United States	29425
434	Prisma Health Cancer Institute - Easley	Easley	South Carolina	United States	29640
435	McLeod Regional Medical Center	Florence	South Carolina	United States	29506
436	Greenville Health System Cancer Institute-Andrews	Greenville	South Carolina	United States	29601
437	Saint Francis Hospital	Greenville	South Carolina	United States	29601
438	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina	United States	29605
439	Prisma Health Cancer Institute - Faris	Greenville	South Carolina	United States	29605
440	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina	United States	29605
441	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina	United States	29615
442	Prisma Health Cancer Institute - Greer	Greer	South Carolina	United States	29650
443	Gibbs Cancer Center-Pelham	Greer	South Carolina	United States	29651
444	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina	United States	29672
445	Spartanburg Medical Center	Spartanburg	South Carolina	United States	29303
446	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
447	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota	United States	57104
448	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
449	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
450	Wellmont Bristol Regional Medical Center	Bristol	Tennessee	United States	37620
451	Wellmont Medical Associates Oncology and Hematology-Bristol	Bristol	Tennessee	United States	37620
452	Regional Cancer Center at Indian Path Community Hospital	Kingsport	Tennessee	United States	37660
453	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee	United States	37660
454	Fredericksburg Oncology Inc	Fredericksburg	Virginia	United States	22401
455	Southwest VA Regional Cancer Center	Norton	Virginia	United States	24273
456	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
457	PeaceHealth Saint John Medical Center	Longview	Washington	United States	98632
458	PeaceHealth Southwest Medical Center	Vancouver	Washington	United States	98664
459	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin	United States	54729
460	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin	United States	54701
461	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301-3526
462	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin	United States	54301
463	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin	United States	54303
464	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin	United States	54303
465	Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
466	Holy Family Memorial Hospital	Manitowoc	Wisconsin	United States	54221
467	Bay Area Medical Center	Marinette	Wisconsin	United States	54143
468	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin	United States	54449
469	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
470	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin	United States	54548
471	ProHealth D N Greenwald Center	Mukwonago	Wisconsin	United States	53149
472	Cancer Center of Western Wisconsin	New Richmond	Wisconsin	United States	54017
473	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin	United States	53066
474	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin	United States	54154
475	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin	United States	54501
476	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin	United States	54868
477	HSHS Saint Nicholas Hospital	Sheboygan	Wisconsin	United States	53081
478	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin	United States	54481
479	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
480	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin	United States	53188
481	Marshfield Clinic-Wausau Center	Wausau	Wisconsin	United States	54401
482	Marshfield Medical Center - Weston	Weston	Wisconsin	United States	54476
483	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin	United States	54494
484	Rocky Mountain Oncology	Casper	Wyoming	United States	82609
485	Cheyenne Regional Medical Center-West	Cheyenne	Wyoming	United States	82001
486	Big Horn Basin Cancer Center	Cody	Wyoming	United States	82414
487	Billings Clinic-Cody	Cody	Wyoming	United States	82414
488	Welch Cancer Center	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Toni K Choueiri, Alliance for Clinical Trials in Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01835158
• Other Study ID Numbers: NCI-2013-00820; NCI-2013-00820; A031203; A031203; A031203; U10CA180821; U10CA031946
• First Posted: Apr 18, 2013
• Last Update Posted: Feb 11, 2021
• Last Verified: Dec 1, 2020

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Kidney Neoplasms; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Arm I (Cabozantinib-s-malate)	Arm II (Sunitinib Malate)
Arm/Group Description	Patients receive 60mg cabozantinib-s-malate PO QD for 6 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.	Patients receive 50mg sunitinib malate PO QD for 4 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	79	78
COMPLETED	78	72
NOT COMPLETED	1	6

Baseline Characteristics

Arm/Group Title	Arm I (Cabozantinib-s-malate)	Arm II (Sunitinib Malate)	Total
Arm/Group Description	Patients receive 60mg cabozantinib-s-malate PO QD for 6 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.	Patients receive 50mg sunitinib malate PO QD for 4 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.	Total of all reporting groups
Overall Participants	79	78	157
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63	64	63
Sex: Female, Male (Count of Participants)
Female	13 16.5%	21 26.9%	34 21.7%
Male	66 83.5%	57 73.1%	123 78.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.3%	0 0%	1 0.6%
Asian	1 1.3%	0 0%	1 0.6%
Native Hawaiian or Other Pacific Islander	1 1.3%	0 0%	1 0.6%
Black or African American	3 3.8%	2 2.6%	5 3.2%
White	70 88.6%	75 96.2%	145 92.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	3 3.8%	1 1.3%	4 2.5%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS)
Description	Progression free survival (PFS) was investigator assessed and is measured from the beginning of treatment until patient progression or death. Progression was determined using RECIST 1.1 criteria, progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).The primary analysis will be based on the stratified log-rank statistic to compare the two treatment arms on PFS. The Kaplan-Meier product-limit estimator will be used to estimate PFS distributions.Progression Free Survival was assessed per investigator, as this was the protocol-specified endpoint, and both investigator and independent review analyses of the PFS endpoint have been published
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

All patients that were enrolled on to study.

Arm/Group Title	Arm I (Cabozantinib-s-malate)	Arm II (Sunitinib Malate)
Arm/Group Description	Patients receive 60mg cabozantinib-s-malate PO QD for 6 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.	Patients receive 50mg sunitinib malate PO QD for 4 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Measure Participants	79	78
Median (95% Confidence Interval) [Months]	8.2	5.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Cabozantinib-s-malate), Arm II (Sunitinib Malate)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95%; .46 to .95
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Overall Survival (OS)
Description	The primary analysis will be based on the stratified log-rank statistic to compare the two treatment arms on OS. The Kaplan-Meier product-limit estimator will be used to estimate OS distributions.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

All enrolled patients

Arm/Group Title	Arm I (Cabozantinib-s-malate)	Arm II (Sunitinib Malate)
Arm/Group Description	Patients receive 60mg cabozantinib-s-malate PO QD for 6 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.	Patients receive 50mg sunitinib malate PO QD for 4 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Measure Participants	79	78
Median (95% Confidence Interval) [Months]	30.3	21.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Cabozantinib-s-malate), Arm II (Sunitinib Malate)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95%; 0.50 to 1.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Objective Response Rates
Description	Objective response rates (ORR) was investigator assessed. ORR is the rate of complete or partial responses, based on RECIST 1.1 criteria. A response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. The Fisher exact test will be used to compare the two treatment arms.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

All enrolled patients.

Arm/Group Title	Arm I (Cabozantinib-s-malate)	Arm II (Sunitinib Malate)
Arm/Group Description	Patients receive 60mg cabozantinib-s-malate PO QD for 6 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.	Patients receive 50mg sunitinib malate PO QD for 4 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Measure Participants	79	78
Number (95% Confidence Interval) [proportion of participants]	0.33 0.4%	0.12 0.2%

Adverse Events

Arm/Group Title	Arm I (Cabozantinib-s-malate)		Arm II (Sunitinib Malate)
Arm/Group Description	Patients receive cabozantinib-s-malate PO QD for 6 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.		Patients receive sunitinib malate PO QD for 4 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	Arm I (Cabozantinib-s-malate)		Arm II (Sunitinib Malate)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (Cabozantinib-s-malate)		Arm II (Sunitinib Malate)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/78 (50%)		39/72 (54.2%)
Blood and lymphatic system disorders
Anemia	2/78 (2.6%)	2	1/72 (1.4%)	1
Blood and lymph sys disorders - Oth Spec	1/78 (1.3%)	1	0/72 (0%)	0
Cardiac disorders
Atrial fibrillation	0/78 (0%)	0	2/72 (2.8%)	2
Palpitations	1/78 (1.3%)	1	0/72 (0%)	0
Endocrine disorders
Hyperthyroidism	1/78 (1.3%)	1	0/72 (0%)	0
Gastrointestinal disorders
Abdominal distension	0/78 (0%)	0	1/72 (1.4%)	1
Abdominal pain	0/78 (0%)	0	1/72 (1.4%)	1
Colitis	0/78 (0%)	0	1/72 (1.4%)	1
Colonic perforation	1/78 (1.3%)	1	0/72 (0%)	0
Constipation	0/78 (0%)	0	1/72 (1.4%)	1
Diarrhea	4/78 (5.1%)	4	5/72 (6.9%)	6
Esophageal pain	1/78 (1.3%)	1	0/72 (0%)	0
Gastric hemorrhage	1/78 (1.3%)	1	1/72 (1.4%)	1
Gastric ulcer	1/78 (1.3%)	1	1/72 (1.4%)	1
Jejunal perforation	1/78 (1.3%)	1	0/72 (0%)	0
Mucositis oral	2/78 (2.6%)	3	1/72 (1.4%)	1
Nausea	2/78 (2.6%)	2	4/72 (5.6%)	5
Pancreatitis	0/78 (0%)	0	1/72 (1.4%)	1
Small intestinal obstruction	0/78 (0%)	0	1/72 (1.4%)	1
Vomiting	1/78 (1.3%)	1	4/72 (5.6%)	5
General disorders
Death NOS	1/78 (1.3%)	1	0/72 (0%)	0
Edema limbs	1/78 (1.3%)	1	0/72 (0%)	0
Fatigue	1/78 (1.3%)	1	5/72 (6.9%)	6
Fever	0/78 (0%)	0	2/72 (2.8%)	2
Pain	2/78 (2.6%)	2	0/72 (0%)	0
Hepatobiliary disorders
Gallbladder pain	1/78 (1.3%)	1	0/72 (0%)	0
Portal vein thrombosis	0/78 (0%)	0	1/72 (1.4%)	1
Infections and infestations
Bladder infection	0/78 (0%)	0	1/72 (1.4%)	1
Encephalitis infection	0/78 (0%)	0	1/72 (1.4%)	1
Lung infection	2/78 (2.6%)	2	0/72 (0%)	0
Nail infection	0/78 (0%)	0	1/72 (1.4%)	1
Sepsis	2/78 (2.6%)	2	1/72 (1.4%)	1
Skin infection	1/78 (1.3%)	1	0/72 (0%)	0
Tooth infection	1/78 (1.3%)	1	0/72 (0%)	0
Injury, poisoning and procedural complications
Fracture	1/78 (1.3%)	1	0/72 (0%)	0
Inj, pois and proced complic - Oth spec	1/78 (1.3%)	1	0/72 (0%)	0
Investigations
Alanine aminotransferase increased	2/78 (2.6%)	3	2/72 (2.8%)	2
Alkaline phosphatase increased	0/78 (0%)	0	1/72 (1.4%)	1
Aspartate aminotransferase increased	1/78 (1.3%)	1	1/72 (1.4%)	1
Blood bilirubin increased	0/78 (0%)	0	1/72 (1.4%)	1
Creatinine increased	2/78 (2.6%)	2	0/72 (0%)	0
ECG QT corrected interval prolonged	0/78 (0%)	0	1/72 (1.4%)	1
Investigations - Other, specify	0/78 (0%)	0	2/72 (2.8%)	2
Lipase increased	0/78 (0%)	0	2/72 (2.8%)	2
Neutrophil count decreased	0/78 (0%)	0	3/72 (4.2%)	3
Platelet count decreased	0/78 (0%)	0	3/72 (4.2%)	3
Serum amylase increased	0/78 (0%)	0	1/72 (1.4%)	1
Weight loss	3/78 (3.8%)	3	0/72 (0%)	0
White blood cell decreased	0/78 (0%)	0	1/72 (1.4%)	1
Metabolism and nutrition disorders
Anorexia	2/78 (2.6%)	2	0/72 (0%)	0
Dehydration	3/78 (3.8%)	3	2/72 (2.8%)	2
Hypercalcemia	1/78 (1.3%)	1	0/72 (0%)	0
Hyperglycemia	1/78 (1.3%)	1	1/72 (1.4%)	2
Hyperkalemia	1/78 (1.3%)	1	1/72 (1.4%)	1
Hypocalcemia	2/78 (2.6%)	2	1/72 (1.4%)	1
Hypoglycemia	0/78 (0%)	0	1/72 (1.4%)	1
Hypokalemia	1/78 (1.3%)	1	0/72 (0%)	0
Hypomagnesemia	2/78 (2.6%)	2	0/72 (0%)	0
Hyponatremia	1/78 (1.3%)	2	2/72 (2.8%)	3
Hypophosphatemia	3/78 (3.8%)	4	3/72 (4.2%)	3
Metabolism, nutrition disord - Oth spec	1/78 (1.3%)	1	0/72 (0%)	0
Arthralgia	1/78 (1.3%)	1	0/72 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	2/78 (2.6%)	2	0/72 (0%)	0
Bone pain	1/78 (1.3%)	1	0/72 (0%)	0
Chest wall pain	1/78 (1.3%)	1	0/72 (0%)	0
Generalized muscle weakness	0/78 (0%)	0	1/72 (1.4%)	1
Pain in extremity	2/78 (2.6%)	2	1/72 (1.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, mal, uncpec - Oth spec	0/78 (0%)	0	1/72 (1.4%)	1
Tumor pain	1/78 (1.3%)	1	0/72 (0%)	0
Nervous system disorders
Dizziness	1/78 (1.3%)	1	1/72 (1.4%)	1
Dysgeusia	0/78 (0%)	0	1/72 (1.4%)	1
Facial muscle weakness	1/78 (1.3%)	1	0/72 (0%)	0
Headache	0/78 (0%)	0	3/72 (4.2%)	3
Hypoglossal nerve disorder	0/78 (0%)	0	1/72 (1.4%)	1
Intracranial hemorrhage	1/78 (1.3%)	1	0/72 (0%)	0
Nervous system disorders - Oth spec	1/78 (1.3%)	1	2/72 (2.8%)	2
Somnolence	0/78 (0%)	0	1/72 (1.4%)	1
Stroke	0/78 (0%)	0	1/72 (1.4%)	1
Syncope	3/78 (3.8%)	3	0/72 (0%)	0
Transient ischemic attacks	0/78 (0%)	0	1/72 (1.4%)	1
Psychiatric disorders
Confusion	1/78 (1.3%)	1	1/72 (1.4%)	1
Depression	2/78 (2.6%)	2	0/72 (0%)	0
Renal and urinary disorders
Acute kidney injury	4/78 (5.1%)	4	2/72 (2.8%)	2
Chronic kidney disease	1/78 (1.3%)	1	1/72 (1.4%)	1
Proteinuria	1/78 (1.3%)	1	1/72 (1.4%)	1
Renal and urinary disorders - Oth spec	1/78 (1.3%)	1	0/72 (0%)	0
Respiratory, thoracic and mediastinal disorders
Bronchial obstruction	0/78 (0%)	0	1/72 (1.4%)	1
Cough	0/78 (0%)	0	1/72 (1.4%)	1
Dyspnea	0/78 (0%)	0	1/72 (1.4%)	1
Pleural effusion	0/78 (0%)	0	2/72 (2.8%)	2
Respiratory failure	0/78 (0%)	0	1/72 (1.4%)	1
Skin and subcutaneous tissue disorders
Alopecia	1/78 (1.3%)	1	0/72 (0%)	0
Palmar-plantar erythrodysesthesia syndrm	4/78 (5.1%)	5	1/72 (1.4%)	1
Skin ulceration	2/78 (2.6%)	2	0/72 (0%)	0
Vascular disorders
Hypertension	8/78 (10.3%)	9	3/72 (4.2%)	3
Hypotension	3/78 (3.8%)	3	1/72 (1.4%)	1
Thromboembolic event	7/78 (9%)	7	1/72 (1.4%)	1
Vascular disorders - Other, specify	1/78 (1.3%)	1	1/72 (1.4%)	1
Vasculitis	1/78 (1.3%)	1	0/72 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm I (Cabozantinib-s-malate)		Arm II (Sunitinib Malate)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	76/78 (97.4%)		68/72 (94.4%)
Blood and lymphatic system disorders
Anemia	29/78 (37.2%)	94	32/72 (44.4%)	103
Blood and lymph sys disorders - Oth Spec	2/78 (2.6%)	3	1/72 (1.4%)	1
Thrombotic thrombocytopenic purpura	1/78 (1.3%)	1	1/72 (1.4%)	1
Cardiac disorders
Atrial fibrillation	2/78 (2.6%)	7	0/72 (0%)	0
Atrial flutter	1/78 (1.3%)	2	0/72 (0%)	0
Heart failure	1/78 (1.3%)	1	0/72 (0%)	0
Palpitations	1/78 (1.3%)	1	0/72 (0%)	0
Sinus bradycardia	2/78 (2.6%)	3	2/72 (2.8%)	3
Sinus tachycardia	1/78 (1.3%)	2	1/72 (1.4%)	1
Ear and labyrinth disorders
Ear and labyrinth disorders - Oth spec	1/78 (1.3%)	2	0/72 (0%)	0
Ear pain	1/78 (1.3%)	2	0/72 (0%)	0
Hearing impaired	1/78 (1.3%)	1	0/72 (0%)	0
Tinnitus	1/78 (1.3%)	5	0/72 (0%)	0
Endocrine disorders
Endocrine disorders - Other, specify	0/78 (0%)	0	1/72 (1.4%)	1
Hyperthyroidism	4/78 (5.1%)	12	2/72 (2.8%)	3
Hypothyroidism	19/78 (24.4%)	50	4/72 (5.6%)	12
Eye disorders
Blurred vision	2/78 (2.6%)	2	2/72 (2.8%)	3
Dry eye	1/78 (1.3%)	1	2/72 (2.8%)	2
Eye disorders - Other, specify	1/78 (1.3%)	1	1/72 (1.4%)	1
Floaters	0/78 (0%)	0	1/72 (1.4%)	2
Glaucoma	1/78 (1.3%)	4	0/72 (0%)	0
Watering eyes	1/78 (1.3%)	1	0/72 (0%)	0
Gastrointestinal disorders
Abdominal distension	0/78 (0%)	0	1/72 (1.4%)	1
Abdominal pain	10/78 (12.8%)	27	8/72 (11.1%)	12
Anal hemorrhage	0/78 (0%)	0	1/72 (1.4%)	2
Anal mucositis	0/78 (0%)	0	1/72 (1.4%)	2
Bloating	2/78 (2.6%)	2	1/72 (1.4%)	1
Colonic obstruction	1/78 (1.3%)	2	1/72 (1.4%)	1
Constipation	16/78 (20.5%)	29	11/72 (15.3%)	15
Dental caries	1/78 (1.3%)	1	0/72 (0%)	0
Diarrhea	54/78 (69.2%)	305	38/72 (52.8%)	96
Dry mouth	16/78 (20.5%)	69	9/72 (12.5%)	14
Dyspepsia	22/78 (28.2%)	56	12/72 (16.7%)	23
Dysphagia	5/78 (6.4%)	8	2/72 (2.8%)	3
Esophagitis	1/78 (1.3%)	1	0/72 (0%)	0
Fecal incontinence	2/78 (2.6%)	18	0/72 (0%)	0
Flatulence	4/78 (5.1%)	26	4/72 (5.6%)	6
Gastritis	0/78 (0%)	0	1/72 (1.4%)	1
Gastroesophageal reflux disease	6/78 (7.7%)	23	6/72 (8.3%)	10
Gastrointestinal disorders - Oth spec	6/78 (7.7%)	9	6/72 (8.3%)	15
Gastrointestinal pain	0/78 (0%)	0	1/72 (1.4%)	1
Gastroparesis	0/78 (0%)	0	1/72 (1.4%)	2
Gingival pain	1/78 (1.3%)	1	0/72 (0%)	0
Hemorrhoids	2/78 (2.6%)	3	0/72 (0%)	0
Mucositis oral	30/78 (38.5%)	63	21/72 (29.2%)	50
Nausea	25/78 (32.1%)	77	26/72 (36.1%)	40
Oral dysesthesia	4/78 (5.1%)	14	2/72 (2.8%)	14
Oral hemorrhage	1/78 (1.3%)	1	0/72 (0%)	0
Oral pain	9/78 (11.5%)	12	5/72 (6.9%)	6
Pancreatitis	2/78 (2.6%)	2	0/72 (0%)	0
Rectal pain	1/78 (1.3%)	1	0/72 (0%)	0
Stomach pain	3/78 (3.8%)	4	1/72 (1.4%)	1
Toothache	2/78 (2.6%)	2	0/72 (0%)	0
Vomiting	18/78 (23.1%)	29	14/72 (19.4%)	21
General disorders
Chills	1/78 (1.3%)	1	4/72 (5.6%)	4
Edema face	2/78 (2.6%)	4	1/72 (1.4%)	3
Edema limbs	7/78 (9%)	38	10/72 (13.9%)	17
Facial pain	2/78 (2.6%)	2	0/72 (0%)	0
Fatigue	65/78 (83.3%)	414	58/72 (80.6%)	215
Fever	3/78 (3.8%)	3	1/72 (1.4%)	1
Flu like symptoms	4/78 (5.1%)	4	3/72 (4.2%)	4
Gait disturbance	1/78 (1.3%)	3	1/72 (1.4%)	3
Gen disord and admin site conds-Oth spec	3/78 (3.8%)	5	5/72 (6.9%)	6
Localized edema	2/78 (2.6%)	2	1/72 (1.4%)	1
Non-cardiac chest pain	2/78 (2.6%)	2	2/72 (2.8%)	2
Pain	8/78 (10.3%)	11	5/72 (6.9%)	12
Sudden death NOS	0/78 (0%)	0	1/72 (1.4%)	1
Immune system disorders
Allergic reaction	1/78 (1.3%)	3	0/72 (0%)	0
Infections and infestations
Bladder infection	0/78 (0%)	0	1/72 (1.4%)	1
Corneal infection	0/78 (0%)	0	1/72 (1.4%)	1
Gum infection	1/78 (1.3%)	1	0/72 (0%)	0
Infections and infestations - Oth spec	5/78 (6.4%)	6	5/72 (6.9%)	6
Lung infection	1/78 (1.3%)	1	0/72 (0%)	0
Mucosal infection	1/78 (1.3%)	1	0/72 (0%)	0
Otitis externa	1/78 (1.3%)	1	0/72 (0%)	0
Papulopustular rash	0/78 (0%)	0	4/72 (5.6%)	5
Paronychia	0/78 (0%)	0	1/72 (1.4%)	1
Pharyngitis	1/78 (1.3%)	1	0/72 (0%)	0
Sinusitis	1/78 (1.3%)	3	1/72 (1.4%)	1
Skin infection	4/78 (5.1%)	6	1/72 (1.4%)	1
Stoma site infection	1/78 (1.3%)	1	0/72 (0%)	0
Tooth infection	1/78 (1.3%)	1	0/72 (0%)	0
Upper respiratory infection	1/78 (1.3%)	2	0/72 (0%)	0
Urinary tract infection	0/78 (0%)	0	4/72 (5.6%)	4
Injury, poisoning and procedural complications
Bruising	4/78 (5.1%)	12	0/72 (0%)	0
Fall	3/78 (3.8%)	3	0/72 (0%)	0
Fracture	1/78 (1.3%)	5	0/72 (0%)	0
Inj, pois and proced complic - Oth spec	2/78 (2.6%)	2	0/72 (0%)	0
Venous injury	1/78 (1.3%)	1	0/72 (0%)	0
Wound complication	1/78 (1.3%)	1	0/72 (0%)	0
Wound dehiscence	0/78 (0%)	0	2/72 (2.8%)	2
Investigations
Activated partial throm time prolonged	1/78 (1.3%)	1	0/72 (0%)	0
Alanine aminotransferase increased	43/78 (55.1%)	135	19/72 (26.4%)	32
Alkaline phosphatase increased	10/78 (12.8%)	17	8/72 (11.1%)	10
Aspartate aminotransferase increased	49/78 (62.8%)	192	23/72 (31.9%)	36
Blood bilirubin increased	11/78 (14.1%)	18	4/72 (5.6%)	8
CD4 lymphocytes decreased	1/78 (1.3%)	1	0/72 (0%)	0
CPK increased	0/78 (0%)	0	1/72 (1.4%)	1
Cholesterol high	2/78 (2.6%)	6	0/72 (0%)	0
Creatinine increased	18/78 (23.1%)	100	16/72 (22.2%)	55
ECG QT corrected interval prolonged	4/78 (5.1%)	6	5/72 (6.9%)	5
Ejection fraction decreased	1/78 (1.3%)	1	0/72 (0%)	0
INR increased	2/78 (2.6%)	7	1/72 (1.4%)	1
Investigations - Other, specify	7/78 (9%)	22	2/72 (2.8%)	2
Lipase increased	2/78 (2.6%)	6	1/72 (1.4%)	1
Lymphocyte count decreased	11/78 (14.1%)	24	14/72 (19.4%)	24
Neutrophil count decreased	12/78 (15.4%)	35	23/72 (31.9%)	93
Platelet count decreased	32/78 (41%)	131	43/72 (59.7%)	103
Serum amylase increased	2/78 (2.6%)	6	0/72 (0%)	0
Weight gain	0/78 (0%)	0	2/72 (2.8%)	3
Weight loss	28/78 (35.9%)	145	12/72 (16.7%)	32
White blood cell decreased	10/78 (12.8%)	39	24/72 (33.3%)	86
Metabolism and nutrition disorders
Anorexia	37/78 (47.4%)	92	23/72 (31.9%)	46
Dehydration	7/78 (9%)	10	6/72 (8.3%)	6
Hypercalcemia	2/78 (2.6%)	2	3/72 (4.2%)	3
Hyperglycemia	16/78 (20.5%)	30	11/72 (15.3%)	47
Hyperkalemia	7/78 (9%)	11	7/72 (9.7%)	9
Hypermagnesemia	0/78 (0%)	0	3/72 (4.2%)	4
Hypernatremia	4/78 (5.1%)	5	1/72 (1.4%)	1
Hypertriglyceridemia	0/78 (0%)	0	1/72 (1.4%)	5
Hyperuricemia	0/78 (0%)	0	1/72 (1.4%)	1
Hypoalbuminemia	17/78 (21.8%)	47	13/72 (18.1%)	19
Hypocalcemia	16/78 (20.5%)	62	10/72 (13.9%)	14
Hypoglycemia	3/78 (3.8%)	4	0/72 (0%)	0
Hypokalemia	13/78 (16.7%)	35	5/72 (6.9%)	5
Hypomagnesemia	19/78 (24.4%)	92	8/72 (11.1%)	20
Hyponatremia	12/78 (15.4%)	25	15/72 (20.8%)	24
Hypophosphatemia	19/78 (24.4%)	62	11/72 (15.3%)	21
Metabolism, nutrition disord - Oth spec	3/78 (3.8%)	6	1/72 (1.4%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	7/78 (9%)	26	6/72 (8.3%)	10
Back pain	8/78 (10.3%)	20	5/72 (6.9%)	7
Bone pain	5/78 (6.4%)	16	2/72 (2.8%)	2
Buttock pain	0/78 (0%)	0	1/72 (1.4%)	1
Chest wall pain	2/78 (2.6%)	3	1/72 (1.4%)	1
Flank pain	1/78 (1.3%)	4	2/72 (2.8%)	3
Generalized muscle weakness	2/78 (2.6%)	7	7/72 (9.7%)	9
Joint range of motion decreased	1/78 (1.3%)	8	0/72 (0%)	0
Muscle weakness lower limb	1/78 (1.3%)	16	2/72 (2.8%)	4
Muscle weakness upper limb	0/78 (0%)	0	1/72 (1.4%)	2
Musculoskeletal, conn tissue - Oth spec	4/78 (5.1%)	33	2/72 (2.8%)	3
Myalgia	7/78 (9%)	52	5/72 (6.9%)	6
Neck pain	2/78 (2.6%)	3	3/72 (4.2%)	3
Pain in extremity	8/78 (10.3%)	16	6/72 (8.3%)	9
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	0/78 (0%)	0	1/72 (1.4%)	1
Nervous system disorders
Ataxia	1/78 (1.3%)	1	0/72 (0%)	0
Concentration impairment	1/78 (1.3%)	2	0/72 (0%)	0
Dizziness	17/78 (21.8%)	32	15/72 (20.8%)	21
Dysgeusia	32/78 (41%)	98	21/72 (29.2%)	58
Dysphasia	2/78 (2.6%)	2	0/72 (0%)	0
Headache	9/78 (11.5%)	22	9/72 (12.5%)	16
Hypersomnia	0/78 (0%)	0	1/72 (1.4%)	1
Memory impairment	3/78 (3.8%)	8	0/72 (0%)	0
Nervous system disorders - Oth spec	3/78 (3.8%)	4	1/72 (1.4%)	1
Neuralgia	0/78 (0%)	0	1/72 (1.4%)	1
Paresthesia	4/78 (5.1%)	14	1/72 (1.4%)	1
Peripheral motor neuropathy	2/78 (2.6%)	6	0/72 (0%)	0
Peripheral sensory neuropathy	8/78 (10.3%)	41	4/72 (5.6%)	4
Somnolence	1/78 (1.3%)	1	0/72 (0%)	0
Syncope	2/78 (2.6%)	2	0/72 (0%)	0
Transient ischemic attacks	0/78 (0%)	0	2/72 (2.8%)	2
Tremor	1/78 (1.3%)	1	0/72 (0%)	0
Psychiatric disorders
Anxiety	7/78 (9%)	13	3/72 (4.2%)	4
Confusion	1/78 (1.3%)	1	1/72 (1.4%)	1
Depression	4/78 (5.1%)	8	4/72 (5.6%)	7
Insomnia	8/78 (10.3%)	13	6/72 (8.3%)	11
Restlessness	1/78 (1.3%)	1	0/72 (0%)	0
Renal and urinary disorders
Acute kidney injury	2/78 (2.6%)	11	1/72 (1.4%)	1
Chronic kidney disease	2/78 (2.6%)	18	4/72 (5.6%)	13
Cystitis noninfective	0/78 (0%)	0	1/72 (1.4%)	2
Hematuria	2/78 (2.6%)	4	2/72 (2.8%)	5
Hemoglobinuria	0/78 (0%)	0	1/72 (1.4%)	2
Proteinuria	6/78 (7.7%)	14	9/72 (12.5%)	12
Renal and urinary disorders - Oth spec	1/78 (1.3%)	3	1/72 (1.4%)	4
Urinary frequency	2/78 (2.6%)	18	2/72 (2.8%)	2
Urinary incontinence	1/78 (1.3%)	4	0/72 (0%)	0
Urinary urgency	0/78 (0%)	0	1/72 (1.4%)	1
Urine discoloration	1/78 (1.3%)	1	0/72 (0%)	0
Reproductive system and breast disorders
Erectile dysfunction	1/78 (1.3%)	4	0/72 (0%)	0
Genital edema	0/78 (0%)	0	1/72 (1.4%)	1
Gynecomastia	0/78 (0%)	0	1/72 (1.4%)	1
Pelvic pain	1/78 (1.3%)	1	0/72 (0%)	0
Testicular pain	0/78 (0%)	0	1/72 (1.4%)	1
Uterine hemorrhage	0/78 (0%)	0	1/72 (1.4%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	2/78 (2.6%)	4	0/72 (0%)	0
Atelectasis	1/78 (1.3%)	1	1/72 (1.4%)	1
Cough	9/78 (11.5%)	17	4/72 (5.6%)	4
Dyspnea	13/78 (16.7%)	33	12/72 (16.7%)	16
Epistaxis	8/78 (10.3%)	9	3/72 (4.2%)	4
Hiccups	2/78 (2.6%)	2	0/72 (0%)	0
Hoarseness	11/78 (14.1%)	32	1/72 (1.4%)	1
Hypoxia	0/78 (0%)	0	1/72 (1.4%)	1
Nasal congestion	2/78 (2.6%)	2	2/72 (2.8%)	3
Pharyngeal hemorrhage	1/78 (1.3%)	5	0/72 (0%)	0
Pleural effusion	1/78 (1.3%)	3	0/72 (0%)	0
Productive cough	6/78 (7.7%)	19	1/72 (1.4%)	1
Resp, thoracic, mediastinal - Oth spec	1/78 (1.3%)	1	1/72 (1.4%)	1
Sleep apnea	0/78 (0%)	0	1/72 (1.4%)	2
Sore throat	5/78 (6.4%)	11	2/72 (2.8%)	2
Voice alteration	8/78 (10.3%)	19	0/72 (0%)	0
Wheezing	2/78 (2.6%)	10	0/72 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	13/78 (16.7%)	42	2/72 (2.8%)	6
Bullous dermatitis	1/78 (1.3%)	1	0/72 (0%)	0
Dry skin	16/78 (20.5%)	50	7/72 (9.7%)	8
Pain of skin	1/78 (1.3%)	1	1/72 (1.4%)	2
Palmar-plantar erythrodysesthesia syndrm	33/78 (42.3%)	119	24/72 (33.3%)	100
Photosensitivity	1/78 (1.3%)	1	0/72 (0%)	0
Pruritus	4/78 (5.1%)	16	4/72 (5.6%)	4
Rash acneiform	12/78 (15.4%)	27	3/72 (4.2%)	3
Rash maculo-papular	14/78 (17.9%)	26	9/72 (12.5%)	19
Skin and subcut tissue disord - Oth spec	16/78 (20.5%)	71	8/72 (11.1%)	17
Skin hyperpigmentation	1/78 (1.3%)	2	1/72 (1.4%)	3
Skin hypopigmentation	2/78 (2.6%)	3	0/72 (0%)	0
Skin ulceration	2/78 (2.6%)	5	2/72 (2.8%)	3
Surgical and medical proced - Oth spec	1/78 (1.3%)	1	0/72 (0%)	0
Vascular disorders
Flushing	1/78 (1.3%)	11	0/72 (0%)	0
Hot flashes	0/78 (0%)	0	2/72 (2.8%)	2
Hypertension	64/78 (82.1%)	328	49/72 (68.1%)	193
Hypotension	5/78 (6.4%)	5	2/72 (2.8%)	2
Peripheral ischemia	1/78 (1.3%)	1	0/72 (0%)	0
Thromboembolic event	1/78 (1.3%)	1	1/72 (1.4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.